The ARFs are a family of 21 kDa GTP-binding regulatory proteins; originally described and purified based on their ability to serve as the protein cofactor required in the in vitro ADP-ribosylation of Gs alpha by cholera toxin. Cloning and sequence analyses of numerous ARF proteins as well as other small (20-25 Kda) GTPbinding proteins has resulted in the description of two structurally distinct families of low molecular weight GTP binding proteins; referred to as the "ras-related" and ARF families. The former is currently comprised of at least thirty distinct gene products. Of all the smaller GTP binding proteins only ARF has a defined biochemical activity, independent of GTP binding or hydrolysis. This activity has allowed the recent delineation of the ARF family into the bona fide ARF proteins and the structurally conserved ARF-related proteins. Recent results indicate that humans express at least three distinct ARF proteins with conserved activities both in vivo and in vitro. One of these human ARF genes, human ARF2, was cloned in a library screen of cDNAs which selected for inserts capable of stimulating the secretion of bFGF. These results are consistent with the observations that ARF is highly concentrated in mammalian cells to the Golgi complex and disruption of ARF1 in yeast results in a secretion defect. The role of ARF in the regulation of growth factor or other protein secretion is being very actively pursued. Specific functional domains of ARF proteins are being mapped with both point and deletion mutations as well as antibody probes. This work has identified a specific region of the protein which is not involved in nucleotide binding but which is critical to ARF function. This has allowed the construction of peptide inhibitors of ARF which are currently being used in in vitro assays of the role of ARF in protein secretion.